Degenerative disc disease (DDD), a cause of chronic lower back pain, is a pathological condition which is accompanied by lower back pain resulting from cracking and cleavage of a disc due to disc degeneration or disc height reduction in response to dehydration of the disc (particularly in nucleus pulposus) with aging. Degenerated disc is characterized by increased abnormal nerve and angiogenesis, and changes in the number and function of cells (cluster formation, necrosis, apoptosis, etc.). One of molecular characteristics of degenerated disc is a decrease of aggrecan. The loss of aggrecan, which plays a crucial role on the disc's load-bearing, results in a drop of disc osmotic pressure, thus being capable of no longer retaining water, which consequently accelerates the existing disc degeneration including the existing annulus fibrosus, and has significant influence on other spinal structures and functions, such as degeneration and hypertrophy of facet joint and ligamentum flavum.
As currently available therapies for pathological chronic lower back pain including these degenerative disc diseases, there are medical therapies including analgesic, exercise rehabilitation therapies, and the like. Unfortunately, these therapeutic approaches suffer from a frequent relapse of the disease, a need for a long period of time and great efforts to treat the concerned disease, and also risk of possible complications due to prolonged medication.
When there is no favorable outcome of the illness even after treatment with such long-term conservative therapy, the patient will inevitably receive surgical therapy. Representative surgical treatments include conventional lumbar fusion surgery involving complete removal of the affected disc tissues and bone graft insertion to the target lesion site, and the recently devised artificial disc insertion. However, these surgical methods have various disadvantages such as being relatively expensive and also potential risk of early and late surgical complications arising from surgery. For example, the lumbar fusion surgery frequently requires periodic redo surgery due to degeneration of adjacent discs. An artificial disc developed to reduce this disadvantage does not provide satisfactory results of long-term follow-up study. So the artificial disc surgery is not commonly performed nowadays. As described above, there is a great difficulty in treating chronic lower back pain due to degenerative disc diseases. To cope with such situations, as an alternative approach to the conservative therapy and surgical therapy, a variety of experimental therapies have been attempted to achieve disc regeneration while minimizing degeneration of the disc itself.
In recent years, there have been tried several biological therapies for treating disc degeneration, e.g., a method which up-regulates the production of important matrix proteins (for example, aggrecan), a method which down-regulates the catabolism induced by pro-inflammatory cytokines (for example, interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-α)) (Ahn, S H et al., Spine 27:911-917, 2002; Burke J G et al., Spine 28:2685-2693, 2003; Kang J D et al., Spine 21:271-277, 1996; Weiler C et al., Spine 30:44-53, 2005; Igarashi T et al., Spine 25:2975-2980, 2000; Olmarker K et al., Spine 23:2538-2544, 1998; Le Maitre C L et al., Arthritis Res Ther 7:R732R745, 2005; and Seguin C A et al., Spine 30:1940-1948, 2005).
These biological therapeutic methods have been performed largely outside the country. The popular method attracting a great deal of interest is direct injection of a bone growth factor (Bone morphogenic protein, BMP) into a disc or transplantation of therapeutic gene-injected disc cells (Masuda K et al., Spine 31:742-745, 2006; Imai Y et al., Spine 32: 1197-1205, 2007; Zhang Y et al., Spine 33:831-838, 2008). However, this method is merely a method of achieving physical changes of a disc structure through physical regeneration, which does not provide relief or removal of pain in patients, and a disc overgrowth, if any, may result in aggravation of neurological conditions due to nerve compression.
Meanwhile, it is known that TGF-beta1 signaling is involved in fibrosis, apoptosis, angiogenesis, tumor cell invasion and metastasis, and the inhibition of TGF-beta1 signaling may be a feasible measure to make treatment of body organ fibrosis, cancer, and/or glomerulosclerosis (Prud'homme G J, Lab Invest 87:1077-1091, 2007).
To this end, there is a need for the development of a new biological material which is effective for degenerative disc disease by promoting disc regeneration while minimizing degeneration of the disc itself, and is capable of treating body organ fibrosis, cancer, glomerulosclerosis, or the like, through the inhibition of TGF-beta1 signaling.